Cannabis Use and CKD: Epidemiological Associations and Mendelian Randomization.

Rationale & Objective: The association between cannabis use and chronic kidney disease (CKD) is controversial. We aimed to assess association of CKD with cannabis use in a large cohort study and then assess causality using Mendelian randomization with a genome-wide association study (GWAS). Study Design: Retrospective cohort study and genome-wide association study. Setting & Participants: The retrospective study was conducted on the All of Us cohort (N=223,354). Genetic instruments for cannabis use disorder were identified from 3 GWAS: the Psychiatric Genomics Consortium Substance Use Disorders, iPSYCH, and deCODE (N=384,032). Association between genetic instruments and CKD was investigated in the CKDGen GWAS (N > 1.2 million). Exposure: Cannabis consumption. Outcomes: CKD outcomes included: cystatin-C and creatinine-based kidney function, proteinuria, and blood urea nitrogen. Analytical Approach: We conducted association analyses to test for frequency of cannabis use and CKD. To evaluate causality, we performed a 2-sample Mendelian randomization. Results: In the retrospective study, compared to former users, less than monthly (OR, 1.01; 95% CI, 0.87-1.18; P = 0.87) and monthly cannabis users (OR, 1.15; 95% CI, 0.86-1.52; P = 0.33) did not have higher CKD odds. Conversely, weekly (OR, 1.28; 95% CI, 1.01-1.60; P = 0.04) and daily use (OR, 1.25; 95% CI, 1.04-1.50; P = 0.02) was significantly associated with CKD, adjusted for multiple confounders. In Mendelian randomization, genetic liability to cannabis use disorder was not associated with increased odds for CKD (OR, 1.00; 95% CI, 0.99-1.01; P = 0.96). These results were robust across different Mendelian randomization techniques and multiple kidney traits. Limitations: Likely underreporting of cannabis use. In Mendelian randomization, genetic instruments were identified in the GWAS that included individuals primarily of European ancestry. Conclusions: Despite the epidemiological association between cannabis use and CKD, there was no evidence of a causal effect, indicating confounding in observational studies.

Reverse pseudohyperkalemia is more than leukocytosis: a retrospective study.

BACKGROUND: Hyperkalemia is a potentially life-threatening electrolyte abnormality that often requires urgent treatment. Clinicians should distinguish true hyperkalemia from pseudohyperkalemia and reverse pseudohyperkalemia (RPK). RPK has exclusively been described in case reports of patients with hematologic malignancies (HMs) and extreme leukocytosis [white blood cell (WBC) count >200 × 103/mL]. METHODS: This single-center retrospective study analyzed laboratory data from the Mount Sinai Data Warehouse between 1 January 2010 and 31 December 2016 for plasma potassium and serum potassium samples drawn within 1 h of each other, with plasma potassium ≥1 mEq/L of the serum potassium. Only plasma potassium ≥5 mEq/L were included. Samples that were documented to be hemolyzed or contaminated were excluded. Clinical history and laboratory data were collected from the identified cases. RESULTS: After applying the inclusion/exclusion criteria to 485 potential cases, the final cohort included 45 cases from 41 patients. There were 24 men and 17 women with a mean age of 52 years. The median plasma potassium was 6.1 mEq/L and serum potassium was 4.4 mEq/L. The median WBC count was 9.35 × 103/mL (interquartile range 6.5-19.7 × 103/mL). Only 44% of the samples had leukocytosis, defined as WBC >11 × 103/mL.Seven patients had a HM and comprised 11 of the cases (24%) with a median WBC of 181.8 × 103µL. There was no difference in their plasma and serum potassium levels when compared with the total cohort, despite a higher median WBC count. Thirty-eight percent of the cases required medical management. CONCLUSIONS: The literature on RPK is limited to case reports and series associated with extreme leukocytosis. This is the first study characterizing RPK predominantly associated with normal leukocyte counts. Further investigation is required to more precisely characterize factors associated with RPK and to elucidate RPK mechanisms.

The nephrologist's guide to cannabis and cannabinoids.

PURPOSE OF REVIEW: Cannabis (marijuana, weed, pot, ganja, Mary Jane) is the most commonly used federally illicit drug in the United States. The present review provides an overview of cannabis and cannabinoids with relevance to the practice of nephrology so that clinicians can best take care of patients. RECENT FINDINGS: Cannabis may have medicinal benefits for treating symptoms of advanced chronic kidney disease (CKD) and end-stage renal disease including as a pain adjuvant potentially reducing the need for opioids. Cannabis does not seem to affect kidney function in healthy individuals. However, renal function should be closely monitored in those with CKD, the lowest effective dose should be used, and smoking should be avoided. Cannabis use may delay transplant candidate listing or contribute to ineligibility. Cannabidiol (CBD) has recently exploded in popularity. Although generally well tolerated, safe without significant side effects, and effective for a variety of neurological and psychiatric conditions, consumers have easy access to a wide range of unregulated CBD products, some with inaccurate labeling and false health claims. Importantly, CBD may raise tacrolimus levels. SUMMARY: Patients and healthcare professionals have little guidance or evidence regarding the impact of cannabis use on people with kidney disease. This knowledge gap will remain as long as federal regulations remain prohibitively restrictive towards prospective research.

Marijuana and Cannabinoids in ESRD and Earlier Stages of CKD.

Marijuana is the most commonly used recreational drug in the United States, and legal recreational and medicinal use has gained public acceptance during the last decade. Twenty-nine US states have established medical marijuana programs, 8 of which have also legalized recreational marijuana, and Canada is expected to legalize recreational marijuana in 2018. Advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) are chronic conditions with significant associated morbidity and mortality. Patients experience substantial symptom burden that is frequently undertreated due to adverse medication side effects. This article reviews the available evidence for the use of medical marijuana to manage chronic pain, nausea/vomiting, anorexia/cachexia, and pruritus, all of which are frequently reported by patients with advanced CKD or ESRD. Potential adverse health effects of medical and recreational marijuana use are also discussed. Regardless of personal, social, and political beliefs, marijuana use is becoming mainstream, and nephrologists should be aware of the potential impact on our patient population. Further research is warranted to investigate the renal endocannabinoid system, the impact of marijuana use on kidney disease outcomes, and the risks and benefits of medical marijuana use on symptoms of advanced CKD and ESRD.